N-Methylmaleimide → (S)-4-{(E)-2-[5-(3-Fluorophenyl)pyridin-2-yl]vinyl}-7-hydroxy-2-methylhexahydro-pyrrolo[3,4-a]pyrrolizine-1,3-dione

HRID 540641Notes

Reaction equation

HRID 540641 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[CH:10][C:11](/[CH:14]=[CH:15]/[CH:16]=O)=[N:12][CH:13]=2)[CH:5]=[CH:6][CH:7]=1.[OH:18][C@@H:19]1[CH2:23][NH:22][C@H:21]([C:24](O)=O)[CH2:20]1.[CH3:27][N:28]1[C:32](=[O:33])C=[CH:30][C:29]1=[O:34]>CC#N>[F:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[CH:10][C:11](/[CH:14]=[CH:15]/[CH:16]3[N:22]4[CH:21]([CH2:20][CH:19]([OH:18])[CH2:23]4)[CH:24]4[C:32](=[O:33])[N:28]([CH3:27])[C:29](=[O:34])[C@H:30]34)=[N:12][CH:13]=2)[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 70261N-MethylmaleimideHCID 440015Cis-4-Hydroxy-L-ProlineHCID 86676729(E)-3-[5-(3-Fluorophenyl)pyridin-2-yl]propenal

Product 1

HCID 86676731(S)-4-{(E)-2-[5-(3-Fluorophenyl)pyridin-2-yl]vinyl}-7-hydroxy-2-methylhexahydro-pyrrolo[3,4-a]pyrrolizine-1,3-dione

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 100 mg of (E)-3-[5-(3-fluorophenyl)pyridin-2-yl]propenal, 64 mg of (2S,4S)-4-hydroxypyrrolidine-2-carboxylic acid, 54 mg of N-methylmaleimide and 4 ml of MeCN is heated at the boil for 4 h. The volatile components are removed under reduced pressure and the residue is purified by column chromatography (silica gel, MeOH:DCM=5:95). In this manner, 4 pure fractions are isolated as racemic mixtures.

Workup

  1. temperatureis heated at the boil for 4 h
  2. customThe volatile components are removed under reduced pressure
  3. customthe residue is purified by column chromatography (silica gel, MeOH:DCM=5:95)
  4. customIn this manner, 4 pure fractions are isolated as racemic mixtures

Sources & evidence

ORD record
ord-3a55be5857774851b18beab5766ec1ca
Source dataset
uspto-grants-2014_10
Patent number
US08871798B2

Reaction notes

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